A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer

NCT01695772 | Completed Phase 4 Results FDA Drug

• 1 other identifier: ML28419
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 7

Brief Summary

This open-label, single arm, multicenter study evaluated the resection rate in participants with colorectal cancer and previously untreated unresectable liver-only metastases after adding bevacizumab to 5-FU based doublet chemotherapy in the neoadjuvant setting. Participants receive standard 5-FU based chemotherapy plus Avastin bevacizumab 5 milligrams per kilogram (mg/kg) every 2 weeks for a maximum of 12 cycles combined pre- and postoperatively, unless they experienced progressive disease or unacceptable toxicity.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving Complete Resection (R0 Resection)

  R0 resection was defined as complete resection confirmed by pathology after pre-operative chemotherapy plus bevacizumab. Participants with R0 resections based on assessments performed at time of surgery, 48 hours post-surgery and 4 and 12 weeks after surgery were reported.

  At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)

Secondary Outcomes (8)

• Percentage of Participants Achieving Incomplete Tumor Resection (R1 Resection)

  At time of surgery (up to 28 weeks), 48 hours post-surgery and 4 and 12 weeks after surgery (up to 40 weeks)

• Percentage of Participants Achieving Objective Response

  Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)

• Number of Participants With Disease Progression or Relapse or Death

  Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)

• Progression Free Survival (PFS)

  Screening until disease progression or death until data cutoff on 12 May 2016 (up to approximately 3.5 years overall)

• Percent Probability (PP) of Being Alive and Progression Free at Months 3, 6, 9, 12, 15, and 18

  Months 3, 6, 9, 12, 15, and 18

Study Arms (1)

Bevacizumab

EXPERIMENTAL

Drug: 5-FU based doublet chemotherapy; Drug: bevacizumab

Interventions

5-FU based doublet chemotherapy DRUG

Standard 5-FU based doublet chemotherapy. Protocol did not specify any particular chemotherapy regimen. The choice of 5-FU based doublet chemotherapy was as per standard of practice and the dosage of 5-FU based doublet chemotherapy was as per product labels.

Bevacizumab

bevacizumab DRUG

5 mg/kg every 2 weeks, up to 12 cycles pre- and postoperatively

Also known as: Avastin

Bevacizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult Chinese participants, 18-75 years of age
• Histologically confirmed adenocarcinoma in colon or rectum with primary lesion surgically removed
• Previously untreated unresectable liver-only metastases
• Liver lesions determined to be unresectable by multidisciplinary team (MDT, consisting of experienced hepatic surgeons, medical oncologist and radiologist).
• No previous treatment against liver metastases, including chemotherapy, surgery, radiotherapy, Transarterial chemoembolisation therapy (TACE) and target therapy
• Adequate hematological, renal and hepatic function
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Life expectancy greater than (\>) 3 months

You may not qualify if:

• The relapse has occurred within 6 months of completion of the adjuvant treatment
• Expected impossible to achieve complete resection (R0 resection) and/or gain 30% residual liver volume even with responsive neoadjuvant therapy
• Participant cannot tolerate the surgery
• Other malignancies in the past 5 years, except for curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
• Any extrahepatic metastases and/or recurrence of the primary tumor
• Any residual toxicity from previous chemotherapy (except alopecia) of National Cancer Institute Common Toxicity Criteria (NCI CTC) v.4.0 grade 2
• Hypertension crisis or encephalopathy
• Pregnant or lactating women
• Clinically significant cardiovascular disease
• Evidence of bleeding diathesis or coagulopathy
• Current or recent (within 10 days of study drug initiation) use of full dose of aspirin, clopidrogel or warfarin
• History or evidence of Central Nervous System (CNS) disease (for example, primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of stroke)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (7)

Beijing Cancer Hospital

Beijing, 100142, China

Location

Sun Yet-sen University Cancer Center

Guangzhou, 510060, China

Location

The Second Affiliated Hospital of Zhejiang University College

Hangzhou, 310009, China

Location

The 2nd Affiliated Hospital of Harbin Medical University

Harbin, 150001, China

Location

Zhongshan Hospital Fudan University

Shanghai, 200032, China

Location

Liaoning cancer Hospital & Institute

Shenyang, 110042, China

Location

Xiehe Hospital, Tongji Medical College Huazhong University of Science & Technology

Wuhan, 430022, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2012
• First Posted: September 28, 2012
• Study Start: October 16, 2012
• Primary Completion: April 4, 2015
• Study Completion: May 12, 2016
• Last Updated: June 9, 2017
• Results First Posted: July 28, 2016

Record last verified: 2017-05

Locations

CN (7)